The effect of several peptide hormones and prostaglandins on normal renal tubular function has been studied extensively. The discovery of cyclic AMP as second messenger of hormone action has advanced our knowledge of their cellular mechanisms of action considerably. Little is known about cAMP function in the glomerulus. It is, however, increasingly becoming apparent that the glomerulus is not just a passive filtration apparatus, but may actively change its filtration characteristics in response to several agents, including peptide hormones, prostaglandins, cAMP and calcium. The glomerulus contains an active, hormone and prostaglandin-responsive adenylate cyclase, and possibly a cyclic GMP system. The role of the cyclic nucleotides in glomerular function is unknown at present. This application is directed toward a more detailed understanding of factors influencing glomerular cyclic nucleotide metabolism and their physiological implications in health and glomerular disease. A second area of interest is the study of defects in the concentrating mechanism in experimental uremia and unilateral ureteral obstruction. These disease models are associated with a vasopressin-hyporesponsiveness of the renal medullary adenylate cyclase and possibly with steps beyond the generation of cAMP. We propose to further examine the cyclic nucleotide systems - cAMP and cGMP - and their physiological role in the glomerulus; to examine in detail the interaction of various agents affecting cyclic nucleotides in the glomerulus and renal medulla; to obtain a preparation of isolated mesangial cells for metabolic and immunological studies; to evaluate the effects of several models of renal disease on glomerular and renal medullary cyclic nucleotide systems.